Continuous processing – already buzz words in pharma a couple of years ago – is still to be adopted fully across the industry. At CPhI Worldwide in Frankfurt last month, a number of companies were talking about their continuous processing offerings and the many advantages they bring.
“It uses less water and less solvents, and produces less waste,” said Pierre Giuliano, Managing Director of La Mesta, a custom manufacturing company located in France. “Continuous pathways can provide better safety and productivity. It also gives us the ability to make compounds that simply could not be made with batch processing.”
“It allows us to deliver more projects in less time,” added Alan Walker, Vice President – Marketing and Development at Kaneka, a Japanese international CDMO based in Osaka.
Of course, these insights are not revelations. Continuous processing has been frequently cited in recent years as a solution to efficiency and flexibility challenges in pharma manufacturing. Continuous processing, it is widely acclaimed, offers ‘process intensification’, is more time-efficient, reduces energy needs, helps to increase productivity and reduces the amount of overall waste.
However, the choice to use continuous processing (rather than batch processing) is not as straightforward as all that. Reaction chemistry, formulation recipe, product demand and overall economics dictate process selection, and the increasing availability of both types of processing facilities means that more and more companies are able to – and having to – make these choices.
Girish Malhotra, President at EPCOT International, writing in this year’s CPhI Annual Report [1], stressed a key difference between batch and continuous processing that influences this decision. With continuous processing, since the process is producing product every operating second, its quality cannot deviate outside the upper and lower quality limits at any instant. The small volumes of milli- or microreactors offer more precise control of reaction parameters, and feedback control loops maintain strict quality regimentation. This avoids batch to batch variations that can arise with batch processing, as well as site to site variations – when you are monitoring every material (from weigh-additions to final dosage weight) at every step and using those data to control every step, there is a good chance that the product from location ‘A’ will be almost identical to that from location ‘B’.
However, deviation outside control limits means the product is not meeting its specifications and this can result in significant financial losses. Therefore, Malhotra suggests that the dominance of batch processing up until now, despite the availability of continuous processing and its dominance in other sectors of the specialty and fine chemicals industry, reflects a focus on profitability over quality. He states, “It is sad but it seems it is due to its sustained profitability even in quality by analysis regimentation.”
He also suggests that there is a general reluctance to adopt unfamiliar manufacturing technology, saying, “Pharma, it seems, due to its own volition has never considered alternate manufacturing technologies.”
This latter suggestion echoes comments by Emil W Ciurczak, President of Doramaxx Consulting, in an article published in Chemicals Knowledge in August last year. Expressing his frustration with the slow uptake of continuous processing in pharma, and the excuses presented by various companies who had “always done it this [batch] way”, he wrote, “If you squint your eyes and look through a pair of reversed binoculars, you can see these arguments applied to the ‘large’ commercial tablet presses in the 1940s, assembly lines for cars in 1905, interchangeable parts for airliners in 1920, and almost any innovation over the last 150 years.”
It is true that not all API ingredients or drug products require the finesse of continuous processing. For many formulations, batch processing is perfectly adequate and fit for purpose. However, in cases where continuous processing can bring positive advantages – espe...
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